Dialysis device

ABSTRACT

A dialysis apparatus for treating a patient with liver and/or kidney disease. In one embodiment a liver dialysis apparatus comprises an artificial liver. The artificial liver comprises a blood compartment, a vegetable protein compartment, and a clear dialysis compartment. In another embodiment the liver dialysis apparatus comprises cartridge made up of at least one layer of vegetable protein. In a further embodiment of the invention a dialysate regeneration device is provided which comprises at least one layer of vegetable protein. The vegetable protein is preferably a soy protein. The soy protein may be unmodified soy protein with urease enzyme activity, modified soy protein with or without urease activity, alone or in combination.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional patent application of patentapplication Ser. No. 10/793,792 filed on Mar. 8, 2004.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

FIELD OF THE INVENTION

This invention relates to dialysis. More specifically, the inventionrelates to a device for treating a patient with liver failure and withminor modification can be used to treat a patient with kidney failure.

BACKGROUND OF THE INVENTION

Treatment options for liver disease are limited. Liver transplantationis the favored treatment for serious liver disease or liver failure.However, the number of suitable liver donors varies and is not alwayssufficient to meet the demand for liver transplant operations. Thus,there is a need for a way to treat patients with liver failure.

A review of the prior art follows.

The topic of artificial livers is discussed in a world wide web (www)article entitled “Artificial Liver” at URL:http://www.organtx.org/bioart/liver.htm. The article notes that ahealthy liver is able to get toxic particles out of the blood byseparating them from a sticky carrier protein called albumin. Thus, ifthe liver fails the toxins stay in the blood and harm nerves, increasepressure in the brain, and damage other important systems. Despite yearsof research, no machine has been able to remove toxins without harmingliver failure patients. One system described is the albumin dialysissystem, where albumin is combined with hollow fibers to remove toxinsfrom the blood of a patient with liver problems. Albumin is an animalprotein that requires extraction from animals. Animals are known to besource of animal diseases that can harm man. Thus, there is a need for anon-animal sticky protein that can act as an absorbent to remove toxinsfrom the blood of a patient with liver disease.

U.S. Pat. No. 5,866,420 issued Feb. 2, 1999 to Talbot et al., describescontinuous cultures of pluripotent parenchymal hepatocytes. Incombination with feeder cells and, optionally, adult pig hepatocytes andmacrophages, the cells are useful in an artificial liver device whichmay be utilized as temporary liver support for mitigating thepathological effects of liver failure. The use of cultures of cells of adifferent genotype, such as pig hepatocytes, raises the prospect ofinter-species disease transfer and the emergence of diseases notpreviously seen in man. A latent virus integrated into the DNA of a pigcell may not show up in a viral screen. Handling and processing cellcultures is complicated and would add to the cost of the treating aliver failure patient. In addition, the '420 patent does not teach orsuggest, for example, using soybean protein to treat blood from apatient with liver disease.

U.S. Pat. No. 6,653,105 issued Nov. 25, 2003 to Triglia et al.,describes a serum-free C3A clonal cell line of possible use in abio-artificial liver device. The '105 cell line is a liver cell linesimilar to the cell line described in U.S. Pat. No. 5,290,684. The cellline exhibits liver-specific activity and may therefore be of use in abio-artificial liver device to treat a patient having or suspected ofhaving a liver condition, liver related disorder or compromised liverfunction resulting either from disease or trauma (e.g. Fulminate hepaticfailure (FHF), awaiting liver transplant or following liver rejectionand awaiting liver retransplant). Maintaining the viability of theserum-free C3A clonal cell line is complicated and requires a high levelof specialist skill not generally found in a liver failure unit in ageneral hospital. Therefore, there is a need for a device to treatpatients with a liver condition, or suspected liver condition, that doesnot rely on maintaining a viable line of liver cells in an artificialenvironment.

U.S. Pub. No. 20030153943 published Aug. 14, 2003 to Michael et al.,describes a medical device, such as a vascular filter, and a method ofmaking the same. The vascular filter is composed of: a reinforcedmembrane unit composed of: a thin filter membrane, and fibers ofreinforcement material embedded in the membrane to strengthen the filterand securely attach the fibers to the membrane. The method offabricating comprises the steps of: providing a mold that can be melted,dissolved, or deformed without damaging membrane material; covering themold with an intermediate material that is easily separated from themembrane material; covering the intermediate material with the membranematerial; placing the fibers in contact with the membrane material thatcovers the intermediate material; covering the fibers with additionalmembrane material to form the membrane with embedded fibers; removingthe mold by melting, dissolving, or deforming the mold; and removing theintermediate material from the membrane. The '943 device and method doesnot teach or suggest, for example, using soybean protein in thetreatment of a patient with actual or suspected liver disease.

U.S. Pat. No. 6,294,380 issued Sep. 25, 2001 to Qiang et al., describesa blood perfusion device used for bioartificial liver support. Humanhepatocyte lines established from normal regenerating liver tissue andmodulated in toxin-challenging conditions are provided. These functionalhepatocytes exhibit extraordinarily enhanced detoxification functions,which are characterized by the elevated glutathione content andglutathione S-transferase activity. A bioreactor is constructed with thefunctional hepatocytes for bioartificial liver support system, whichincludes perfusion inlets and perfusion outlets, a containment vessel, acentrifugal pump and macroporous microcarriers where the functionalhepatocytes are grown. Relying on human hepatocyte lines to treat aliver patient's blood is complicated and requires a high level ofspecialist skill.

U.S. Pat. No. 3,972,818 issued Aug. 3, 1976 to Bokros, describes adevice for treating human blood prior to its return to a living humanbody. The blood filter employs a bed of fibers between about 1 and 100microns in diameter, the outer surface of which is formed of impermeablecarbon. Suitable fibrous substrates may be coated with vapor-depositedpyrolytic carbon, and the fibers may be supported between similarlycoated upper and lower screens. The '818 device does not teach orsuggest the subject matter of the present invention.

None of the above inventions and patents, taken either singly or incombination, is seen to describe the present invention as claimed.

SUMMARY OF THE INVENTION

The invention is directed to a dialysis apparatus for treating a patientwith liver and/or kidney disease. In one embodiment a liver dialysisapparatus comprises an artificial liver. The artificial liver comprisesa blood compartment, a vegetable protein compartment, and a cleardialysis compartment. In another embodiment the liver dialysis apparatuscomprises cartridge made up of at least one layer of vegetable protein.In a further embodiment of the invention a dialysate regeneration deviceis provided which comprises at least one layer of vegetable protein. Thevegetable protein is preferably a soy protein. The soy protein may beunmodified soy protein with urease enzyme activity, modified soy proteinwith or without urease activity, alone or in combination.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an environmental perspective view of a mobile liver dialysisdevice integrated into the design of a belt according to the presentinvention.

FIG. 2 is an environmental perspective view of a compact sized liverdialysis device according to the present invention.

FIG. 3A is a schematic representation of a liver dialysis deviceaccording to the present invention.

FIG. 3B shows a partially cut-away view of an artificial liver accordingto one aspect of the present invention.

FIG. 3C is a schematic representation of an artificial liver thatcomprises more than one blood compartment.

FIG. 4A is a schematic representation of a dialysis system that employsan unconventional dialysate regeneration cartridge according to thepresent invention.

FIG. 4B shows a partially cut away view of a dialyzer of conventionaldesign.

Similar reference characters denote corresponding features consistentlythroughout the attached drawings.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Specific structural and functional details disclosed hereby are not tobe interpreted as limiting, but merely as providing a proper basis forthe claims and as a representative basis for teaching one of ordinaryskill in the art how to practice the invention.

The present invention is particularly directed to a device thatcomprises at least one layer of vegetable protein for removing toxicagents from the blood of a patient with a dysfunctional liver and/ordysfunctional kidney. The vegetable protein may be substantiallyunmodified or chemically modified with or without urease enzymeactivity. The vegetable protein is preferably a legume protein derivedfrom the seeds of leguminous plants such as soybean, cottonseed, peanut,tung nut, castor bean, and linseed, alone or in combination.

In one embodiment of the invention, the protein is substantiallyunmodified soy protein containing active urease enzyme. In anotherembodiment of the invention, the protein is chemically modified soyprotein substantially free of urease enzyme activity. In a still furtherembodiment of the invention, the soy protein is chemically modified soyprotein with added urease enzyme activity.

Soybean is known to be a very healthy legume that contains a high amountof healthy protein that is not normally toxic to man and is necessarilysubstantially free of animal or liver related disease agents such as thecausative agent of hepatitis. Soy protein offers a far safer alternativeto animal or human albumin that could harbor undesirable disease agents.

Vegetable protein such as soy protein is made up of amino acids linkedtogether to form a three dimensional structure. At least some of thevegetable protein amino acids are hydrophilic such as the serine andthreonine amino acids. At least some of the vegetable protein aminoacids are hydrophobic such as phenylalanine, leucine and isoleucine.Other amino acids may be charged such as aspartate and lysine, which atphysiological pH are respectively negatively and positively charged.(The ionic states of amino acid side chains as a function of pH arefound, for example, on page 14 in Chemical Modification Of Proteins(Authors: Gary E. Means and Robert E. Feeney, publisher: San Francisco,Holden-Day [1971], ISBN: 0-81625-561-X, Library of Congress Catalog CardNumber: 74-140785).

The vegetable amino acids are able to bind to molecules by means of avariety of non-covalent intermolecular binding interactions includinghydrogen bonding and other electrostatic interactions, hydrophobicbonding, and non-polar Van der Waal interactions. For example, an aminoacid with a side-chain that exhibits a net negative charge has a strongaffinity for a liver toxic molecule with a positive charge. Conversely,a vegetable amino acid with a side chain having a positive charge at aspecific pH (e.g., lysine) would bind to a liver toxic molecule with anegative charge. Amino acids with non-polar aliphatic side chains suchas leucine, isoleucine and valine would tend to non-covalently bind tohydrophobic molecules or hydrophobic parts of molecules. Thus, avegetable protein molecule comprises of numerous residues, i.e. aminoacid side-chains, which are available for binding to toxic molecules.

To render more of the amino-acid side chains of the soy proteinmolecules available to bind to toxic molecules, the soy protein can bechemically modified in vitro to modify the binding properties ofspecific side-chains; disulfide bond breaking agents, such as thereducing agent ammoniumthioglycolate (ATG), may be used to break —S—S—bonds to help denature the soy protein molecules to expose internalamino acids for binding to toxic molecules. Other methods of alteringthe shape of soy protein are well known and include alkaline hydrolysis,which also breaks the protein backbone at random points to producevariable length soy polypeptides.

Since it is important that the dialysate is not contaminated with lowmolecular weight soy polypeptides (for example, under 10,000 Daltons)the amount of hydrolysis should be limited. SDS polyacrylamide gelelectrophoresis (SDS-PAGE) along with appropriate molecular weightmarkers can be used to check the size distribution of the hydrolyzed Soyprotein. Unsuitable polypeptide lengths can be selectively discardedusing established techniques such as dialysis based on, for example,permeable membranes with molecular weight cut-offs of around 10,000Daltons to remove the unwanted lower molecular Soy molecules.

It will be understood that the molecular weight of the unwantedpolypeptides can vary according to the molecular weight cut-offs of thepermeable membranes used in the invention. For example, if the membraneshave a 5,000 Dalton cut-off, the unsuitable molecular weight range wouldbe less than about 5,000 Daltons. Thus, the invention is not restrictedto making use of peptides of greater than 10,000 Daltons, but may makeuse of lower molecular weight peptides based on the cut-off of themembranes used in the dialysis apparatus according to the invention.

In addition to breaking —S—S— bonds, the vegetable protein may befurther chemically modified using a variety of known techniques andreagents. The terms “chemically modified” or “chemical modification” areused herein to encompass any treatment, such as hydrolysis,carboxylation, oxidation, precipitation or additional separation, whichoccurs after the vegetable protein material is extracted. The field ofchemical modification of proteins is well known in the art and isreviewed, for example, in: (1) Gary E. Means and Robert E. Feeney inChemical Modification Of Proteins (publisher: San Francisco, Holden-Day(1971), ISBN: 0-81625-561-X, Library of Congress Catalog Card Number:74-140785); (2) Nashef et al., Effects of Alkali on Proteins, Disulfidesand Their Products, J. Agric. Food Chem., Vol. 25, No. 2, (1977), pp245-251; and (3) McKinney and Uhing, Carboxymethylated Soybean Protein,J. Amer. Oil Chem. Soc., Vol. 36, No. 2, (1959), pp 49-51. The Means andFeeney, Nashef, and McKinney references are hereby incorporated byreference in their entirety.

Isolated unmodified soy protein may be prepared by selecting dehulledsoybeans that are cracked and flaked for extraction of oil by means ofsolvent. The oil extraction process and subsequent removal of solventfrom the flakes are carried out without undesirable alteration of theprotein present in the flakes. To isolate the unmodified protein, 1 partof substantially oil-free flakes is slurried with 10 to 20 parts ofwater and a small amount of alkali is added to increase the solubilityof the soy protein. The solution containing the extracted protein isthen usually separated from the flake residue by means of shakerscreens. The screened solution is subjected to filtration orcentrifugation to remove flake fines, and the protein is precipitatedfrom the solution, in the isoelectric range of the protein (usually inthe pH range of about 4.0 to 4.5), by means of acid. The protein curdsobtained are dewatered and dried to provide unmodified soy protein.Specifically, after the isoelectric precipitation step the unmodifiedsoy protein curd can be dried to produce a granulated dried protein ofgreater than 95% purity. Typically, this soy isolate, which has nototherwise been heated or chemically modified in some fashion, willcontain a significant amount of urease enzyme activity, which is aninherent component of uncooked or unmodified soy protein. The naturalurease activity enables the soy protein to convert urea into ammonia,and may be used in the invention as described below. For furtherinformation see, for example, U.S. Pat. No. 4,352,692 (issued Oct. 5,1982 to Krinski et al); the '692 patent is hereby incorporated byreference in its entirety. In addition, the manufacture and chemistry ofisolated soy protein is discussed in chapters five and six of the TAPPIMonograph Series-No. 9 (PROTEIN and SYNTHETIC ADHESIVES for PaperCoating, TAPPI Monograph Series-No. 9, (1952), pp 84-108); chapters fiveand six are herein incorporated by reference in their entirety.

Urease enzyme activity can also be maintained in soy protein that hasbeen modified by adding urease to the modified protein. For example, thesoy protein may be oxidized and provided with urease activity bycarrying out the following steps: (1) forming a slurry of a ureasecontaining unmodified soy protein with a proteinaceous solids content of10 to 30% by weight; (2) adding to the slurry a sufficient amount ofurea to react with the urease therein to produce ammonia sufficient toincrease the pH of the slurry to a value above about pH 8.0; (3) addingan oxidizing agent to the slurry in an amount and for a time sufficientto improve the rheological properties by lowering the viscosity of theprotein material; and (4) adding urease enzyme back into the oxidized(i.e., modified) slurry to provide a modified soy protein slurry withurease activity; and (5) gently drying the modified urease containingsoy protein slurry for later incorporation into a liver or kidneydialysis device of the present invention. If the modified soy protein isintended to treat a patient with abnormal liver function and normalkidney function, the modified soy protein need not contain ureaseactivity; therefore, step (4) may be skipped, i.e. urease enzyme neednot be added to the modified soy protein. In addition, the types of soyprotein may be mixed, e.g. modified with unmodified soy protein. Thus,it should be clear that the soy protein component may vary in form:unmodified urease containing soy protein, modified soy protein lackingurease activity, modified soy protein with urease activity, alone or incombination. It will be understood that the handling and processing ofthe soy protein should be undertaken to meet the appropriate legalstandards, including but not limited to: use of a clean facility, andpracticing where possible aseptic technique to avoid contaminating thesoy protein with undesirable matter.

Referring now to the figures.

FIG. 1 shows one embodiment of the present invention. Specifically, aliver dialysis device 100 (represented by the alpha-numeric label “100a”) is shown integrated into a belt 120 that can be worn by a patient140 with liver disease or suspected liver disease. Visible in the belt120 is an artificial liver 160, a regeneration device 180 that purifiesthe dialysis liquid (dialysate), and a power supply 200. Tubes 220 and240 provide appropriate arterial and venous access between theartificial liver 160 and the patient 140. If necessary, theextracorporeal transport of the patient's blood through tubes 220 and240 may be assisted by a blood pump 380 (see FIG. 3A); the blood flowrate should be at least about 250 milliliters per minute (ml/min), andpreferably in the range between about 250 ml/min and about 500 ml/min.

FIG. 2 shows another embodiment of the present invention. Specifically,a liver dialysis device 100 (represented by the alpha-numeric label “100b”) is shown integrated into a housing 260. The device 100 b is shownpositioned next to a liver patient 140.

FIG. 3A is a schematic representation of a liver dialyzer device 100(represented by the alpha-numeric label “100 c”). An artificial liver160 is shown comprising at least one blood compartment 280, a soyprotein compartment 300, and a clear dialysis compartment 320. A firstselectively permeable membrane 340 separates compartments 280 and 300. Asecond selectively permeable membrane 360 separates compartments 300 and320. The membranes 340 and 360 may be in any suitable form, for instancein that of flat or tubular film (see FIG. 3B), or it may comprise alarge number of hollow fibers. The blood compartment 280 is connected tothe circulatory system of a patient 140 by means of tubes 220 and 240.If necessary, the extracorporeal transport of the blood may be assistedby a blood pump 380. The blood pump 380 may be integrated into thedesign of, for example, the artificial liver 160.

Dialysis liquid flows through compartment 320 and circulates through adialysis circuit 400 by means of a dialysate pump 420. Dialysate enterscompartment 300 from compartment 320 thereby allowing an interchangeacross membrane 340. The molecular weight of the protein moleculesinside compartment 300 are such that they are unable to penetratemembranes 340 or 360, but smaller molecules that don't bind to theprotein are able to transfer across membrane 340 and into circuit 400for selective removal by the dialysate regeneration device 180.

It should be understood that the exact arrangement and layout of theartificial liver 160 might vary. For example, FIG. 3C shows anartificial liver 160 (shown as 160 a), wherein the tube 220 directspatient blood to more than one blood compartment 280 (shown as 280 a,280 b, and 280 c). Since volume increases by the cube and surface areaby the square the ratio of surface area to volume ratio is morefavorable as volume decreases. Thus, the rate of exchange acrossmembrane 340 improves with lower cross section area of the at least oneblood compartment 280. However, the cross section area of the at leastone blood compartment 280 should be sufficient not to obstruct the flowof blood through blood compartment 280.

It will be understood that the order and arrangement of the variousfunctional members in the dialysis circuit 400 may vary. For example,the dialysate pump 420 may be integrated into the design of theregeneration device 180. The location of the flow meter 500 may alsovary without detracting from the spirit of the present invention.

It should be understood that the term “clear” as used in “clear dialysiscompartment 320” is intended to mean “substantially clear of soyprotein”; the membrane 360 serves to allow the interchange of dialysatebetween the compartments 300 and 320 while preventing transfer of soyprotein molecules from soy protein compartment 300 into clear dialysatecompartment 320; incidentally, membrane 340 prevents transfer of soyprotein molecules from soy protein compartment 300 into bloodcompartment 280. Toxic molecules from the blood compartment 280 transferinto the soy protein compartment 300 for absorption by the soy proteinheld therein, toxic molecules not absorbed are free to transfer acrossmembrane 360 into the clear dialysate compartment 320 which forms partof the dialysate circuit 400.

The membrane 340 is rated to be impermeable to blood cells, includingwhite and red blood cells, but is permeable to electrolytes andmolecules up to about 10,000 Daltons. The membrane 360 is preferablypermeable to electrolytes and molecules up to about 10,000 Daltons;however, the molecular weight cut-offs of the membranes 340 and 360 canbe dissimilar. Also, the membranes 340 and 360 may be dissimilar and mayseparately take the form of a flat or tubular film, or hollow fibers.Waste products not absorbed by the soy protein in compartment 300 aretransferred across the membrane 360 into the clear dialysate compartment320. The soy protein may be unmodified soy protein with urease activity,modified protein with urease activity, and modified protein absenturease activity, alone or in combination. It is preferred that if thepatient 140 is not suffering from kidney failure (i.e. liver failureabsent kidney failure) the soy protein is modified protein absent ureaseactivity.

Still referring to FIG. 3A, dialysis circuit 400 comprises aregeneration device 180 adapted to purify the dialysate (dialysisliquid) from the waste products it has taken up from compartment 300.More specifically, the device 180 converts used dialysate back into“fresh” or reconstituted dialysate. The regeneration device 180 mayconsist of several layers connected in series or in parallel, which eachserve to eliminate one or more waste products. The cartridge may be ofconventional design such as the REDY™ purification cartridge as used inthe REDY™ dialysis system. The REDY™ purification cartridge comprisesfive layers through which used dialysate passes: (i) a purificationlayer comprising of activated charcoal; (ii) an enzyme layer comprisingof urease; (iii) a cation exchange layer comprising of zirconium oxide;(iv) and anion exchange layer comprising of hydrated zirconium oxide;and (v) an absorbent layer comprising again of activated charcoal.Organon Teknika Corporation of Oklahoma City, Okla., USA, supplies theREDY™ dialysis system. Alternatively, the regeneration device 180 maycomprise a layer of vegetable protein such as soy protein (unmodified,modified with or without urease enzyme activity, alone or incombination); the layer of vegetable protein may replace or act as apartial substitute for the activated charcoal layer normally found inconventional dialysate regeneration cartridges such as that used in theREDY™ dialysis system. The layers in device 180 may be in series or inparallel.

When urease enzyme activity is present in the vegetable protein incompartment 300 the regeneration device 180 need not have a layercomprising of urease enzyme. Specifically, when the vegetable protein isunmodified vegetable protein with urease activity and/or modifiedprotein with added urease activity there is no requirement for aseparate layer of urease activity in device 180. For example, theregeneration device 180 may comprise of four layers: (i) a purificationlayer comprising of activated charcoal; (ii) a cation exchange layercomprising of zirconium oxide; (iii) and anion exchange layer comprisingof hydrated zirconium oxide; and (iv) an absorbent layer comprisingagain of activated charcoal. Preferably the charcoal layers are left outor diminished in device 180; for example, the regeneration device 180may be made of just three layers: (i) a cation exchange layer comprisingof zirconium oxide; (ii) an anion exchange layer comprising of hydratedzirconium oxide; and (iii) a layer comprising activated charcoal.

Where ammonia remains a problem due to urease activity an ammoniascavenger may be incorporated into device 180, e.g. as a separate layercomprising of ammonia scavenger or mixed with another layer in device180. Any suitable ammonia scavenger may be used such as a particulatemagnesium phosphate product as described in U.S. Pat. No. 4,650,587(issued Mar. 17, 1987 to Polak et al) with the general formula(Mg)_(x)(H)_(y) (PO₄)_(z), wherein when “z” has an assigned value of 1,“x” has a value greater than 1, and about 1.1 to about 1.3, and “y” hasa value less than 1 and about 0.4 to about 0.8; the '587 reference ishereby incorporated by reference in its entirety.

Still referring to FIG. 3A, in the dialysis circuit 400 there are: adialysate pump 420, an optional vessel 440 to hold reconstituteddialysate, dialysate temperature probe 460, a dialysate heater 480, anda flow meter 500. It should be understood that the order of devices inthe circuit 400 may vary; additionally, the devices may be integratedinto single functional members, e.g., the temperature probe 460 andheater 480 might be integrated and operated under the control of adedicated temperature controller. The terms “reconstituted dialysate”and “fresh dialysate” are regarded as equivalent terms.

The devices 420, 460, 480, 500 are monitored and/or operated by acontroller 520 adapted to perform logic operations based on a controlalgorithm. For example, the controller 520 monitors and controls thefunction of the pump 420 (in response to data received from, forexample, the flow meter 500), and heater 480 is switched on or off (inresponse to data received from the temperature probe 460). A powersupply 200 is connected to all parts that require power such as, forexample, the controller 520 and dialysate pump 420.

FIG. 4A is a schematic representation of a further embodiment of thepresent invention 100 d employing a novel dialysate regenerationcartridge 180 a; the cartridge 180 a comprises at least one layer ofvegetable protein such as soy protein. The dialysate regenerationcartridge 180 a is used in conjunction with a dialyzer of conventionaldesign (represented by the alpha-numeral “160 b”). The conventionaldialyzer 160 b operates much in the same way as an artificial kidney asdescribed in column 6, lines 44-56 in U.S. Pat. No. 4,213,859 (issuedJul. 22, 1980 to Smakman et al); the '859 patent is hereby incorporatedby reference in its entirety.

FIG. 4B shows a partially cut away view of dialyzer 160 b. Dialyzer 160b has a blood compartment 280 and a clearance or dialysis compartment320 separated by a selectively permeable membrane 365. The membrane 365may be in any desirable form, for instance in that of flat or tubularfilm, or it may be a large number of hollow fibers. Dialysis liquidflows through compartment 300 and circulates through the dialysiscircuit 400 as shown in FIG. 4A.

The dialysate regeneration device 180 a comprises at least one layer ofvegetable protein. The vegetable protein may be unmodified or modifiedsoy protein with or without urease enzyme activity. The layer ofvegetable protein may replace or complement a charcoal layer as found inthe REDY™ purification cartridge. For example, the dialysateregeneration cartridge 180 a may comprise of the following layers: (i) alayer of vegetable protein; (ii) a cation exchange layer comprising ofzirconium oxide; (iii) and anion exchange layer comprising of hydratedzirconium oxide; and (iv) a layer comprising of activated charcoal.

The composition of the layer of vegetable protein in cartridge 180 a mayvary. Cartridge 180 a may comprise a layer of modified or unmodified soyprotein with or without urease enzyme activity. The layer of vegetableprotein may be made of a combination of modified and unmodified soyprotein with or without urease enzyme activity. The order of layers withrespect to dialysate flow may vary, though it is preferable to have apurification layer downstream of the cation and anion exchange layers,e.g. a layer of activated charcoal downstream of the ion exchangelayers. Dialysate regeneration device 180 a enables a conventionaldialyzer 160 b to be used to treat a patient 140 with liver and/orkidney disease.

It is to be understood that the present invention is not limited to theembodiments described above, but encompasses any and all embodimentswithin the scope of the following claims.

1. A dialysate regeneration device, comprising: at least one cationexchange layer; at least one anion exchange layer; and at least oneabsorbent layer, wherein the at least one absorbent layer comprises avegetable protein.
 2. The dialysate regeneration device according toclaim 1 further comprising a layer of activated charcoal.
 3. Thedialysate regeneration device according to claim 1, wherein thevegetable protein is essentially unmodified soy protein with ureaseactivity.
 4. The dialysate regeneration device according to claim 1,wherein the vegetable protein is essentially unmodified soy protein withurease activity, and wherein the dialysate regeneration device furthercomprises an ammonia scavenger compound.
 5. The dialysate regenerationdevice according to claim 1, wherein the vegetable protein is modifiedsoy protein lacking urease enzyme activity.
 6. The dialysateregeneration device according to claim 1, wherein the vegetable proteinis modified soy protein in combination with active urease enzyme capableof converting urea into ammonia.